Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish.
Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish.
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三唑类杀菌剂诱导斑马鱼脂肪生成并抑制成骨细胞生成。
DOI：
10.1093/toxsci/kfad031
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Bondesson,Maria
中科院分区：
文献类型：
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作者：
Thrikawala,Savini;Mesmar,Fahmi;Bhattacharya,Beas;Muhsen,Maram;Mukhopadhyay,Srijita;Flores,Sara;Upadhyay,Sanat;Vergara,Leoncio;Gustafsson,Jan-Åke;Williams,Cecilia;Bondesson,Maria
三唑类是唑类杀真菌剂的主要类别，通常用于农业、兽医和人类医学。母体暴露于某些三唑类抗真菌药物会导致先天性畸形，包括骨骼畸形。我们假设，在农业中用作杀虫剂的三唑也会造成发育中胚胎骨骼畸形的风险。在这项研究中，三种常用的三唑类杀菌剂，环唑醇，多效唑，三唑醇的致畸作用进行了研究，在斑马鱼，Danio rerio。暴露于三唑类杀菌剂引起发育中的斑马鱼幼虫的骨和软骨畸形。来自环唑醇全胚胎转录组学的数据表明，暴露于该化合物诱导脂肪形成，同时抑制骨骼发育。证实了这一发现，通过定量PCR测定，所选骨和软骨标记基因的表达随着三唑暴露而显著下调。所选脂肪形成基因的表达被三唑上调。此外，暴露于三个三唑诱导脂肪形成和脂滴形成在体外3 T3-L1前脂肪细胞。在体内斑马鱼幼虫，环唑醇暴露引起脂质积累。这些结果表明，暴露于三唑促进脂肪形成的骨骼发育为代价，因此，他们扩大了真正的骨脂肪转换的化学基团。
Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish,Danio rerio.Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formationin vitroin 3T3-L1 pre-adipocyte cells.In vivoin zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.